Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
1998-10-27
2001-05-08
Criares, Theodore J. (Department: 1617)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S663000, C514S397000
Reexamination Certificate
active
06228864
ABSTRACT:
TECHNICAL FIELD
This invention relates generally to methods and pharmaceutical compositions for treating sexual dysfunction; more particularly, the invention relates to treatment of premature ejaculation, such as by administration of compounds that are 5-HT (serotonin) receptor agonists and antagonists.
BACKGROUND
Premature maculation is a debilitating sexual dysfunction. This dysfunction can lead to an inability to enter or sustain relationships and can cause psychological damage to sufferers. Premature ejaculation can also impair reproductive success.
Previous methods of treating premature ejaculation include psychological therapies, topical anesthetics and the use of devices (U.S. Pat. Nos. 5,535,758, 5,063,915, 5,327,910, and 5,468,212). All of these methods have significant drawbacks. Psychological therapies benefit only a subset of patients and require specialized therapists who may not be available to all patients, particularly in remote areas. Furthermore, psychological therapies cannot alleviate premature ejaculation resulting from non-psychological causes. Anesthetic agents decrease sensitivity of tissues, thereby diminishing sexual pleasure. Also, topical anesthetics can be transferred to sexual partners and thereby decrease their sensitivity and pleasure as well. With regard to devices, these can be awkward, inconvenient and embarrassing to use. Devices are highly conspicuous, and reveal the very condition which the suffering partner may prefer to conceal. Additionally, devices can cause irritation to one or both partners.
Methods for treating premature ejaculation by systemic administration of several different antidepressant compounds have been described (U.S. Pat. Nos. 4,507,323, 4,940,731, 5,151,448, and 5,276,042; PCT Publication No. W
0
95/13072). However, these drugs may not be effective for all patients, and the side effects of these drugs can halt treatment or impair patient compliance. Disease states or adverse interactions with other drugs may contraindicate the use of these compounds or require lower dosages that may not be effective to delay the onset of ejaculation. Additionally, the stigma of mental illness associated with antidepressant therapy can discourage patients from beginning or continuing such treatments.
Administration of the antidepressant fluoxetine has been claimed to treat premature ejaculation (U.S. Pat. No. 5,151,448). However, the administration of fluoxetine has many undesired aspects. Patients with hepatic or renal impairments may not be able to use fluoxetine due to its metabolism in the liver and excretion via the kidney. Systemic events during fluoxetine treatment involving the lungs, kidneys or liver have occurred, and death has occurred from overdoses. In addition, side effects of oral fluoxetine administration include hair loss, nausea, vomiting, dyspepsia, diarrhea, anorexia, anxiety, nervousness, insomnia, drowsiness, fatigue, headache, tremor, dizziness, convulsions, sweating, pruritis, and skin rashes. Fluoxetine interacts with a range of drugs, often by impairing their metabolism by the liver.
U.S. Pat. No. 4,940,731 describes the oral or parenteral administration of sertraline for treating premature ejaculation. It has been recognized that sertraline shares many of the same problems as fluoxetine; see Martindale,
The Extra Pharmacopoeia,
31st edition, at p. 333 (London: The Royal Pharmaceutical Society, 1996). Sertraline is metabolized in the liver, and is excreted in the urine and feces. Thus, patients with cirrhosis must take lower doses, and caution must be exercised when administering sertraline to patients with renal impairment. Individuals taking monoamine oxidase inhibitors cannot take sertraline due to the risk of toxicity, leading to memory changes, confusion, irritability, chills, pyrexia and muscle rigidity. Side effects resulting from oral sertraline administration include nausea, diarrhea, dyspepsia, insomnia, somnolence, sweating, dry mouth, tremor and mania. Rare instances of coma, convulsions, fecal incontinence and gynecomastia have occurred in patients undergoing sertraline therapy.
U.S. Pat. No. 5,276,042 describes the administration of paroxetine for the treatment of premature ejaculation. Paroxetine is predominantly excreted in the urine, and decreased doses are recommended in patients with hepatic and renal impairments. Like sertraline, paroxetine cannot be given to patients undergoing treatment with a monoamine oxidase inhibitor. Side effects from oral administration of paroxetine include hyponatremia, asthenia, sweating, nausea, decreased appetite, oropharynx disorder, somnolence, dizziness, insomnia, tremor, anxiety, impaired micturition, weakness and paresthesia.
Thus there is a need for a method of treating premature ejaculation that requires no specialized psychological therapy, can be used conveniently and without embarrassment, and does not involve the problems associated with prior therapeutic methods.
Serotonin, or 3-(&bgr;-aminoethyl)-5-hydroxyindole (5-hydroxytryptophan, or “5-HT”) is a neurotransmitter in the central nervous system which is known to play an important role in the pathogenesis of affective illness. Several different 5-HT receptor types have been identified, including 5-HT
1
, 5-HT
2
and 5-HT
3
, which are further divided into a number of different subtypes, e.g., 5-HT
1A
, 5-HT
1B
, 5-HT
1D
, 5-HT
1E
and 5-HT
1F
. It has now been discovered that administration of various serotonin agonists and antagonists is quite effective in the treatment of premature ejaculation, and addresses a number of the above-noted deficiencies in the art. Accordingly, in a preferred embodiment, the present invention is directed to the administration of serotonin agonists and antagonists, preferably 5-HT
3
receptor antagonists (also referred to herein as “5-HT
3
antagonists”) and 5-HT
4
receptor agonists (also referred to herein as “5-HT
4
agonists”), in the treatment of premature ejaculation. In alternative embodiments, the invention is also directed to the treatment of premature ejaculation using other types of active agents, including adrenergic neurone blockers and adrenergic agonists and antagonists.
SUMMARY OF THE INVENTION
Accordingly, it is a primary object of the invention to address the above-described need in the art by providing a novel method for treating premature ejaculation by administering an effective amount of a serotonin antagonist or agonist to an individual in need of such therapy.
It is another object of the invention to provide such a method wherein the pharmacologically active agent is administered orally.
It is a further object of the invention to provide such a method wherein the pharmacologically active agent is administered parenterally.
It is another object of the invention to provide such a method wherein the pharmacologically active agent is administered buccally.
It is also an object of the invention to provide such a method wherein the pharmacologically active agent is administered nasally.
It is another object of the invention to provide such a method wherein the pharmacologically active agent is administered transurethrally.
It is an additional object of the invention to provide such a method wherein the pharmacologically active agent is administered via intracavernosal injection.
It is another object of the invention to provide a novel method for treating premature ejaculation by locally administering an effective amount of a pharmacologically active agent to an individual in need of such therapy, wherein the active agent is an antidepressant drug, a serotonin antagonist or agonist (as above), an adrenergic neurone blocker, or an adrenergic agonist or antagonist.
It is yet a further object of the invention to provide pharmaceutical formulations for carrying out the aforementioned methods.
It is another object of the invention to provide a kit capable of use by an individual in carrying out the aforementioned methods.
Additional objects, advantages and novel features of the invention will be set forth in part in the description which follows, and in p
Doherty, Jr. Paul C.
Place Virgil A.
Smith William L.
Criares Theodore J.
Reed Dianne E.
Reed & Associates
Vivus Inc.
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